Psilocibina e neuroplasticidade: novas perspectivas terapêuticas para depressão resistente

Autores

DOI:

https://doi.org/10.19180/1809-2667.v28n22026.23658

Palavras-chave:

neuroplasticidade, depressão resistente, Psilocibina, terapia psicodélica, neurociência

Resumo

A depressão é um transtorno mental multifatorial e uma das principais causas de incapacidade global. Parte dos pacientes não responde aos antidepressivos convencionais, caracterizando a depressão resistente ao tratamento (DRT). Este estudo investigou o potencial terapêutico da psilocibina na DRT, com foco em seus efeitos sobre a neuroplasticidade. Realizou-se revisão integrativa nas bases PubMed, Scielo e Cochrane Library, incluindo estudos publicados entre 2019 e 2026. Os resultados indicam que a psilocibina aumenta a expressão do fator neurotrófico derivado do cérebro (BDNF), estimula o crescimento de espinhos dendríticos e promove reorganização sináptica em regiões como córtex pré-frontal e hipocampo. Ensaios clínicos demonstram melhora significativa e sustentada dos sintomas depressivos após uma ou duas administrações, especialmente associadas à psicoterapia. Conclui-se que a psilocibina é uma alternativa promissora para DRT, embora sejam necessários mais estudos e regulamentação para garantir seu uso seguro e eficaz.

Downloads

Os dados de download ainda não estão disponíveis.

Biografia do Autor

  • Leticia de Almeida Castro
    Bacharel em Farmácia pela Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: leticia.acastro@hotmail.com. 
  • André Luiz dos Anjos Simões Júnior
    Bacharel em Farmácia pela Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: luizandre07@icloud.com.
  • Guilherme Gianizeli Corradi Simões
    Bacharel em Farmácia pela Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: corradiguilherme@gmail.com. 
  • Vagner Rocha Simonin de Souza, Faculdade Multivix Vila Velha
    Doutor em Ciências, com ênfase em Química Biológica, pela Universidade Federal do Rio de Janeiro (UFRJ). Professor na Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: vagner.souza@multivix.edu.br.
  • Lucas Luís Meigre Dias Pereira, Faculdade Multivix Cariacica
    Mestre em Engenharia Ambiental pela Universidade Federal do Espírito Santo (UFES). Professor na Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: lucas.pereira@multivix.edu.br.
  • Ariely Lirio de Sousa Lacerda, Faculdade Multivix Vila Velha
    Mestranda em Ciências Farmacêuticas pela Universidade Vila Velha (UVV). Professora na Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: arielylirio@gmail.com. 
  • Cristiane Lyrio da Silva, Faculdade Multivix Vila Velha
    Doutora em Biotecnologia Vegetal pela Universidade Vila Velha (UVV). Professora na Faculdade Multivix Vila Velha ‒ Vila Velha, ES ‒ Brasil. E-mail: cristianesilva16@professor.multivix.edu.br.

Referências

AGRAWAL, M.; BEAUSSANT, Y.; SHNAYDER, S.; AMELI, R.; RODDY, K.; STEVENS, N.; RICHARDS, B.; SCHOR, N.; HONSTEIN, H.; JENKINS, B.; BATES, M.; THAMBI, P. Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder. Cancer, v. 130, n. 7, p. 1137-1146, 2024. DOI: https://doi.org/10.1002/cncr.35010. Disponível em: https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35010. Acesso em: 8 nov. 2025.

AL-HARBI, K. S. Treatment-resistant depression: risk factors, biology, and treatment strategies. Neuropsychiatric Disease and Treatment, v. 8, p. 17-26, 2012. DOI: https://doi.org/10.2147/PPA.S29716. Disponível em: https://www.dovepress.com/treatment-resistant-depression-therapeutic-trends-challenges-and-futur-peer-reviewed-fulltext-article-PPA. Acesso em: 5 abr. 2025.

APA. AMERICAN PSYCHIATRIC ASSOCIATION. Diagnostic and Statistical Manual of Mental Disorders. 5. ed. Arlington: APA, 2014.

APKARIAN, V. A.; HASHMI, J. A.; BALIKI, M. N. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain, v. 152, Suppl 3, S49-S64, 2010. DOI: https://doi.org/10.1016/j.pain.2010.11.010. Disponível em: https://www.ovid.com/jnls/pain/abstract/10.1016/j.pain.2010.11.010~pain-and-the-brain-specificity-and-plasticity-of-the-brain?redirectionsource=fulltextview. Acesso em: 15 maio 2025.

BARRETT, F. S.; DOSS, M. K.; SEPEDA, N. D.; PEKAR, J. J.; GRIFFITHS, R. R. Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention. NeuroImage, v. 218, p. 116980, 2020. DOI: https://doi.org/10.1016/j.neuroimage.2020.116980. Disponível em: https://www.nature.com/articles/s41598-020-59282-y. Acesso em: 8 nov. 2025.

BECK, J. S. Terapia cognitivo-comportamental: teoria e prática. Porto Alegre: Artmed, 2011.

BECKER, A. M.; HOLZE, F.; GRANDINETTI, T.; KLAIBER, A.; TOEDTLI, V. E.; KOLACZYNSKA, K. E.; DUTHALER, U.; VARGHESE, N.; ECKERT, A; GRÜNBLATT, E.; LIECHTI, M. E. Acute effects of psilocybin after escitalopram or placebo pretreatment in a randomized, double-blind, placebo-controlled crossover study in healthy subjects. Clinical Pharmacology & Therapeutics, v. 111, n. 4, p. 886-895, 2022. DOI: https://doi.org/10.1002/cpt.2487. Disponível em: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2487. Acesso em: 8 nov. 2025.

BERK, M.; KÖHLER-FORSBERG, O.; TURNER, M.; PENNINX B. W. J. H.; WROBEL, A.; FIRTH, J.; LOUGHMAN, A.; REAVLEY, N. J.; MCGRATH, J. J.; MOMEN, N. C.; PLANA-RIPOLL, O.; O'NEIL, A.; SISKIND, D.; WILLIAMS, L. J.; CARVALHO, A. F.; SCHMAAL, L.; WALKER, A. J.; DEAN, O.; WALDER, K.; BERK, L.; DODD, S.; YUNG, A. R.; MARX, W. Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management. World Psychiatry, v. 22, n. 3, p. 366-387, 2023. DOI: https://doi.org/10.1002/wps.21110. Disponível em: https://onlinelibrary.wiley.com/doi/10.1002/wps.21110. Acesso em: 31 maio 2025.

BERLIM, M. T.; VAN DEN EYNDE, F.; DASKALAKIS, Z. J. A systematic review and meta-analysis on the efficacy and acceptability of bilateral repetitive transcranial magnetic stimulation (rTMS) for treating major depression. Psychological Medicine, v. 43, n. 11, p. 2245-2254, 2013. Disponível em: https://www.cambridge.org/core/journals/psychological-medicine/article/abs/systematic-review-and-metaanalysis-on-the-efficacy-and-acceptability-of-bilateral-repetitive-transcranial-magnetic-stimulation-rtms-for-treating-major-depression/521131BC1EB008D0C607CCC4BE3961ED. Acesso em: 25 mar. 2025.

BLISS, T. V. P.; LØMO, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. Journal of Physiology, v. 232, n. 2, p. 331-356, 1973. Disponível em: https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.1973.sp010273. Acesso em: 3 jun. 2025.

BRENNER, P.; TAIPALE, H.; JOSEFSSON, P.; DIBERNARDO, A.; TANSKANEN, A; MITTENDORFER-RUTZ, E.; REUTFORS, J. Desfechos psiquiátricos e incapacidade escolar e laboral a longo prazo em filhos de pais com depressão e depressão resistente ao tratamento. Soc Psychiatry Psychiatr Epidemiol, v. 61, p. 423-434, 2026. DOI: https://doi.org/10.1007/s00127-025-02988-z. Disponível em: https://link.springer.com/article/10.1007/s00127-025-02988-z. Acesso em: 8 nov. 2025.

CARHART-HARRIS, R. L. Translational challenges in psychedelic medicine. New England Journal of Medicine, v. 388, n. 5, p. 476-477, 2023. DOI: https://doi.org/10.1056/NEJMcibr2213109. Disponível em: https://www.nejm.org/doi/10.1056/NEJMcibr2213109. Acesso em: 8 nov. 2025.

CARHART-HARRIS, R. L.; BOLSTRIDGE, M.; DAY, C. M. J.; RUCKER, J.; WATTS, R.; ERRITZOE, D. E.; KAELEN, M.; GIRIBALDI, B.; BLOOMFIELD, M.; PILLING, S.; RICKARD, J. A.; FORBES, B.; FEILDING, A.; TAYLOR, D.; CURRAN, H. V.; NUTT, D. J. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, v. 235, n. 2, p. 399-408, 2018. DOI: https://doi.org/10.1007/s00213-017-4771-x. Disponível em: https://link.springer.com/article/10.1007/s00213-017-4771-x. Acesso em: 11 jun. 2025.

CARHART-HARRIS, R. L.; CHANDARIA, S.; ERRITZOE, D. E.; GAZZALEY, A.; GIRN, M.; KETTNER, H.; MEDIANO, P. A. M.; NUTT, D. J.; ROSAS, F. E.; ROSEMAN, L.; TIMMERMANN, C.; WEISS, B.; ZEIFMAN, R. J.; FRISTON, K. J. Canalization and plasticity in psychopathology. Neuropharmacology, v. 226, p. 109398, 2023. DOI: https://doi.org/10.1016/j.neuropharm.2022.109398. Disponível em: https://www.sciencedirect.com/science/article/pii/S0028390822004579. Acesso em: 8 nov. 2025.

CARVALHO, S.; GONÇALVES, Ó. F.; BRUNONI, A. R.; FERNANDES-GONÇALVES, A.; FREGNI, F.; LEITE, J. Transcranial direct current stimulation as an add-on treatment to cognitive-behavior therapy in first episode drug-naïve major depression patients: the ESAP study protocol. Frontiers in Psychiatry, v. 11, p. 563058, 2020. DOI: https://doi.org/10.3389/fpsyt.2020.563058. Disponível em: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.563058/full. Acesso em: 8 nov. 2025.

CASTRÉN, E.; RANTAMÄKI, T. The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Developmental Neurobiology, v. 70, n. 5, p. 289-297, 2010. DOI: https://doi.org/10.1002/dneu.20758. Disponível em: https://onlinelibrary.wiley.com/doi/10.1002/dneu.20758. Acesso em: 11 jun. 2025.

CATLOW, B. J.; SONG, S.; PAREDES, D. A.; KIRSTEIN, C. L.; SANCHEZ RAMOS, J. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Experimental Brain Research, v. 228, n. 4, p. 481-491, 2013. DOI: https://doi.org/10.1007/s00221-013-3579-0. Disponível em: https://link.springer.com/article/10.1007/s00221-013-3579-0. Acesso em: 19 maio 2026.

CHU, A.; WADHWA, R. Selective serotonin reuptake inhibitors. In: STATPEARLS [Internet]. Treasure Island (FL): StatPearls Publishing, 2026. Atualizado em: 1 maio 2023. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK554406/.Acesso em: 11 jun. 2025.

COELHO, A. C. Fatores determinantes de qualidade de vida física e mental em pacientes com doença pulmonar intersticial: uma análise multifatorial. 2009. Dissertação (Mestrado em Ciências Médicas) – Universidade Federal do Rio Grande do Sul, Porto Alegre, 2009. Disponível em: https://www.lume.ufrgs.br/handle/10183/16359. Acesso em: 4 set. 2025.

COSENZA, R. M.; GUERRA, L. B. Neurociência e educação: como o cérebro aprende. Porto Alegre: Artmed, 2011.

DAVIS, A. K.; BARRETT, F. S.; SO, S.; GUKASYAN, N.; SWIFT, T. C.; GRIFFITHS, R. R. Development of the Psychological Insight Questionnaire among a sample of people who have consumed psilocybin or LSD. Journal of Psychopharmacology, v. 35, n. 4, p. 437-446, 2021a. DOI: https://doi.org/10.1177/0269881120967878. Disponível em: https://journals.sagepub.com/doi/10.1177/0269881120967878. Acesso em: 3 jun. 2025.

DAVIS, A. K.; BARRETT, F. S.; MAY, D. G.; COSIMANO, M. P.; SEPEDA, N. D.; JOHNSON, M. W.; FINAN, P. H.; GRIFFITHS, R. R. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry, v. 78, n. 5, p. 481-489, 2021b. DOI: https://doi.org/10.1001/jamapsychiatry.2020.3285. Disponível em: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2772630. Acesso em: 18 abr. 2025.

DAVIS, A. K.; LEVIN, A. W.; NAGIB, P. B.; ARMSTRONG, S. B.; LANCELOTTA, R. L. Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD. BMJ Open, v. 13, n. 5, e068884, 2023. DOI: https://doi.org/10.1136/bmjopen-2022-068884. Disponível em: https://bmjopen.bmj.com/content/13/5/e068884. Acesso em: 11 maio 2025.

DAVOUDIAN, P. A.; SHAO, L. X.; KWAN, A. C. Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin. ACS Chemical Neuroscience, v. 14, n. 3, p. 468-480, 2023. DOI: https://doi.org/10.1021/acschemneuro.2c00637. Disponível em: https://pubs.acs.org/doi/10.1021/acschemneuro.2c00637. Acesso em: 8 nov. 2025.

DELGADO, P. L. Depression: the case for a monoamine deficiency. The Journal of clinical psychiatry, v. 61, Suppl 6, p. 7-11, 2000. Disponível em: https://pubmed.ncbi.nlm.nih.gov/10775018/. Acesso em: 19 maio 2026.

DOSS, M. K.; POVAŽAN, M.; ROSENBERG, M. D.; SEPEDA, N. D.; DAVIS, A. K.; FINAN, P. H.; SMITH, G. S.; PEKAR, J. J.; BARKER, P. B.; ROLAND R. GRIFFITHS, R. R.; BARRETT, F. S. Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry, v. 11, n. 1, 574, 2021. DOI: https://doi.org/10.1038/s41398-021-01706-y. Disponível em: https://www.nature.com/articles/s41398-021-01706-y. Acesso em 8 nov. 2025.

DRAGANSKI, B.; GASER, C.; KEMPERMANN, G.; KUHN, H. G.; WINKLER, J.; BUCHEL, C.; MAY, A. Temporal and spatial dynamics of brain structure changes during extensive learning. Journal of Neuroscience, v. 26, n. 23, p. 6314-6317, 2006. DOI: https://doi.org/10.1523/JNEUROSCI.4628-05.2006. Disponível em: https://www.jneurosci.org/content/26/23/6314. Acesso em: 5 abr. 2025.

DUMAN, R. S.; AGHAJANIAN, G. K. Synaptic dysfunction in depression: potential therapeutic targets. Science, v. 338, n. 6103, p. 68-72, 2012. DOI: https://doi.org/10.1126/science.1222939. Disponível em: https://www.science.org/doi/10.1126/science.1222939. Acesso em: 11 jun. 2025.

FISHER, E. L.; SMITH, R.; CONN, K.; CORCORAN, A. W.; MILTON, L. K.; HOHWY, J.; FOLDI, C. J. Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats. Translational Psychiatry, v. 14, n. 1, 394, 2024. DOI: https://doi.org/10.1038/s41398-024-03103-7. Disponível em: https://www.nature.com/articles/s41398-024-03103-7. Acesso em: 8 nov. 2025.

GADDIS, A.; LIDSTONE, D. E.; NEBEL, M. B.; GRIFFITHS, R. R.; MOSTOFSKY, S. H.; MEJIA, A. F.; BARRETT, F. S. Corrigendum to “Psilocybin induces spatially constrained alterations in thalamic functional organization and connectivity”. NeuroImage, v. 274, 120130, 2023. DOI: https://doi.org/10.1016/j.neuroimage.2023.120130. Disponível em: https://www.sciencedirect.com/science/article/pii/S1053811923002811. Acesso em: 8 nov. 2025.

GAO, K.; ORUC, E. B.; KOPARAL, B. Pharmacological monotherapy for depressive disorders: current and future – a narrative review. Medicina, v. 61, n. 4, 558, 2025. DOI: https://doi.org/10.3390/medicina61040558. Disponível em: https://www.mdpi.com/1648-9144/61/4/558. Acesso em: 8 nov. 2025.

GIRN, M.; ROSEMAN, L.; BERNHARDT, B.; SMALLWOOD, J.; CARHART-HARRIS, R.; SPRENG, R. N. Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex. NeuroImage, v. 256, 119220, 2022. DOI: https://doi.org/10.1016/j.neuroimage.2022.119220. Disponível em: https://www.sciencedirect.com/science/article/pii/S1053811922003445. Acesso em: 8 nov. 2025.

GLENNON, R. A.; DUKAT, M.; GRELLA, B.; HONG, S-S.; COSTANTINO, L.; TEITLER, M.; SMITH, C.; EGAN, C.; DAVIS, K.; MATTSON, M. V. Binding of beta-carbolines and related agents at serotonin, dopamine and benzodiazepine receptors. Drug and Alcohol Dependence, v. 60, n. 2, p. 121-132, 2000. DOI: https://doi.org/10.1016/S0376-8716(99)00148-9. Disponível em: https://www.sciencedirect.com/science/article/pii/S0376871699001489. Acesso em: 8 nov. 2025.

GOLDEN, C. T.; CHADDERTON, P. Psilocybin reduces low-frequency oscillatory power and phase synchrony in the anterior cingulate cortex of awake rodents. Scientific Reports, v. 12, 12702, 2022. DOI: https://doi.org/10.1038/s41598-022-16325-w. Disponível: https://www.nature.com/articles/s41598-022-16325-w. Acesso em: 8 nov. 2025.

GOMEZ-PINILLA, F.; HILLMAN, C. The influence of exercise on cognitive abilities. Comprehensive Physiology, v. 3, n. 1, p. 403-428, 2013. DOI: https://doi.org/10.1002/cphy.c110063. Disponível em: https://onlinelibrary.wiley.com/doi/10.1002/j.2040-4603.2013.tb00485.x. Acesso em: 8 nov. 2025.

GOODWIN, G. M.; CROAL, M.; FEIFEL, D.; KELLY, J. R.; MARWOOD, L.; MISTRY, S.; O’KEANE, V.; PECK, S. K.; SIMMONS, H.; SISA, C.; STANSFIELD, S. C.; TSAI, J.; WILLIAMS, S.; EKATERINA MALIEVSKAIA, E. Psilocybin for treatment-resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology, v. 48, n. 10, p. 1492-1499, 2023. DOI: https://doi.org/10.1038/s41386-023-01648-7. Disponível em: https://www.nature.com/articles/s41386-023-01648-7. Acesso em: 8 nov. 2025.

GRANDJEAN, J.; BUEHLMANN, D.; BUERGE, M.; SIGRIST, H.; SEIFRITZ, E.; VOLLENWEIDER, F. X.; PRYCE, C. R.; RUDIN; M. Psilocybin exerts distinct effects on resting-state networks associated with serotonin and dopamine in mice. NeuroImage, v. 225, 117456, 2021. DOI: https://doi.org/10.1016/j.neuroimage.2020.117456. Disponível em: https://www.sciencedirect.com/science/article/pii/S1053811920309411. Acesso em: 8 nov. 2025.

GRIFFITHS, R. R.; JOHNSON, M. W.; CARDUCCI, M. A.; UMBRICHT, A.; RICHARDS, W. A.; RICHARDS, B. D.; COSIMANO, M. P.; KLINEDINST, M. A. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, v. 30, n. 12, p. 1181-1197, 2016. DOI: https://doi.org/10.1177/0269881116675513. Disponível em: https://journals.sagepub.com/doi/10.1177/0269881116675513. Acesso em: 8 nov. 2025.

GUKASYAN, N.; DAVIS, A. K.; BARRETT, F. S.; COSIMANO, M. P.; SEPEDA, N. D.; JOHNSON, M. W.; GRIFFITHS, R. R. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: prospective 12-month follow-up. Journal of Psychopharmacology, v. 36, n. 2, p. 151-158, 2022. DOI: https://doi.org/10.1177/02698811211073759. Disponível em: journals.sagepub.com/doi/pdf/10.1177/02698811211073759. Acesso em: 8 nov. 2025.

GUZMÁN, G. Hallucinogenic mushrooms in Mexico: an overview. Economic Botany, v. 62, n. 3, p. 404-412, 2008. Disponível em: https://www.jstor.org/stable/40390479. Acesso em: 19 maio 2026.

HESSELGRAVE, N.; TROPPOLI, T. A.; WULFF, A. B.; COLE, A. B.; THOMPSON, S. M. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2 receptor activation in mice. Proceedings of the National Academy of Sciences, v. 118, n. 17, e2022489118, 2021. DOI: https://doi.org/10.1073/pnas.2022489118. Disponível em: https://www.pnas.org/doi/full/10.1073/pnas.2022489118. Acesso em: 8 nov. 2025.

HOFMANN, A.; TROXLER, F. Identification of psilocin. Experientia, v. 15, n. 3, p. 101-102, 1959. DOI: https://doi.org/10.1007/BF02166696. Disponível em: https://link.springer.com/article/10.1007/BF02166696. Acesso em: 8 nov. 2025.

HOLLON, S. D.; DERUBEIS, R. J.; SHELTON, R. C.; AMSTERDAM, J. D.; SALOMON, R. M.; O’REARDON, J. P.; LOVETT, M. L.; YOUNG, P. R.; HAMAN, K. L.; FREEMAN, B. B.; GALLOP, R. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Archives of General Psychiatry, v. 62, n. 4, p. 417-422, 2005. DOI: https://doi.org/10.1001/archpsyc.62.4.417. Disponível em: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/208447. Acesso em: 8 nov. 2025.

HOWLAND, R. H. Atypical antipsychotics are not all alike: side effects and risk assessment. Journal of Psychosocial Nursing and Mental Health Services, v. 52, n. 9, p. 13-15, 2014. DOI: https://doi.org/10.3928/02793695-20140820-01. Disponível: https://journals.healio.com/doi/10.3928/02793695-20140820-01. Acesso em: 8 nov. 2025.

JOHNSON, M. W.; GRIFFITHS, R. R. Potential therapeutic effects of psilocybin. Neurotherapeutics, v. 14, n. 3, p. 734-740, 2017. DOI: https://doi.org/10.1007/s13311-017-0542-y. Disponível em: https://www.sciencedirect.com/science/article/pii/S1878747923014514. Acesso em: 8 nov. 2025.

JOHNSON, M. W.; RICHARDS, W. A.; GRIFFITHS, R. R. Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology, v. 22, n. 6, p. 603-620, 2008. DOI: https://doi.org/10.1177/0269881108093587. Disponível em: https://journals.sagepub.com/doi/epdf/10.1177/0269881108093587. Acesso em: 4 abr. 2025.

KOLB, B.; GIBB, R. Brain plasticity and behaviour in the developing brain. Journal of the Canadian Academy of Child and Adolescent Psychiatry, v. 20, n. 4, p. 265-276, 2011. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC3222570/. Acesso em: 4 abr. 2025.

KRISHNAN, V.; NESTLER, E. J. The molecular neurobiology of depression. Nature, v. 455, p. 894-902, 2008. DOI: https://doi.org/10.1038/nature07455. Disponível em: https://www.nature.com/articles/nature07455. Acesso em: 4 abr. 2025.

LABATE, B. C.; GOULART, S. L. O uso de plantas psicoativas nas Américas. Rio de Janeiro: Gramma, 2019.

LOUBINOUX, I.; BRIHMAT, N.; CASTEL-LACANAL, E.; MARQUE, P. Cerebral imaging of post-stroke plasticity and tissue repair. Revue Neurologique, v. 173, n. 9, p. 577-583, 2017. DOI: https://doi.org/10.1016/j.neurol.2017.09.007. Disponível em: https://www.sciencedirect.com/science/article/pii/S0035378717307348. Acesso em: 4 abr. 2025.

LY, C.; GREB, A. C.; CAMERON, L. P.; WONG, J. M.; BARRAGAN, E. V.; WILSON, P. C.; KYLE F. BURBACH, K. F.; ZARANDI, S. S.; SOOD, A.; MICHAEL R. PADDY, M. R.; DUIM, W. C.; DENNIS, M. Y.; MCALLISTER, A. K.; ORI-MCKENNEY, K. M.; GRAY, J. A.; OLSON, D. E. Psychedelics promote structural and functional neural plasticity. Cell Reports, v. 23, n. 11, p. 3170-3182, 2018. DOI: https://doi.org/10.1016/j.celrep.2018.05.022. Disponível em: https://www.sciencedirect.com/science/article/pii/S2211124718307551. Acesso em: 4 abr. 2025.

MADSEN, M. K.; FISHER, P. M.; BURMESTER, D.; DYSSEGAARD, A.; STENBÆK, D. S.; KRISTIANSEN, S.; JOHANSEN, S. S.; LEHEL, S.; LINNET, K.; SVARER, C.; ERRITZOE, D.; OZENNE, B.; KNUDSEN, G. M. Correction: Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology, v. 44, n. 7, p. 1336-1337, 2019. DOI: https://doi.org/10.1038/s41386-019-0360-5. Disponível em: https://www.nature.com/articles/s41386-019-0360-5. Acesso em: 8 nov. 2025.

MASON, N. L.; KUYPERS, K. P. C.; RECKWEG, J. T.; MÜLLER, F.; TSE, D. H. Y.; RIOS, B. DA; TOENNES, S. W.; STIERS, P.; FEILDING, A.; RAMAEKERS, J. G. Spontaneous and deliberate creative cognition during and after psilocybin exposure. Translational Psychiatry, v. 11, n. 1, 209, 2021. DOI: https://doi.org/10.1038/s41398-021-01335-5. Disponível em: https://www.nature.com/articles/s41398-021-01335-5. Acesso em: 8 nov. 2025.

MCINTYRE, R. S; ALSUWAIDAN, M.; BAUNE, B. T.; BERK, M.; DEMYTTENAER, K.; GOLDBERG, J. F.; GORWOOD, P.; HO, R.; KASPER, S.; KENNEDY, S. H.; LY-USON, J.; MANSUR, R. B.; MCALLISTER-WILLIAMS, R. H.; MURROUGH, J. W.; NEMEROFF, C. B.; NIERENBERG, A. A.; ROSENBLAT, J. D.; SANACORA, G.; SCHATZBERG, A. F.; SHELTON, R.; STAHL, S. M.; TRIVEDI, M. H.; VIETA, E.; VINBERG, M.; WILLIAMS, N.; YOUNG, A. H.; MAJ, M. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry, v. 22, n. 3, p. 394–412, 2023. DOI: https://doi.org/10.1002/wps.21120. Disponível em: https://www.nature.com/articles/s41398-021-01335-5. Acesso em: 8 nov. 2025.

MILLER, A. H.; RAISON, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology, v. 16, n. 1, p. 22-34, 2016. DOI: https://doi.org/10.1038/nri.2015.5. Disponível em: https://www.nature.com/articles/nri.2015.5. Acesso em: 4 abr. 2025.

MOLINER, R.; GIRYCH, M.; BRUNELLO, C. A.; KOVALEVA, V.; BIOJONE, C.; ENKAVI, G.; ANTENUCCI, L.; KOT, E. F.; GONCHARUK, S. A.; KAURINKOSKI, K.; KUUTTI, M.; FRED, S. M.; ELSILÄ, L. V.; SAKSON, S.; CANNAROZZO, C.; DINIZ, C. R. A. F.; SEIFFERT, N.; RUBIOLO, A.; HAAPANIEMI, H.; MESHI, E.; NAGAEVA, E.; ÖHMAN, T.; RÓG, T.; KANKURI, E.; VILAR, M.; VARJOSALO, M.; KORPI, E. R.; PERMI, P.; MINEEV, K. S.; SAARMA, M.; VATTULAINEN, I.; CASAROTTO, P. C.; CASTRÉN, E. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, v. 26, p. 1032-1041, 2023. DOI: https://doi.org/10.1038/s41593-023-01316-5. Disponível em: https://www.nature.com/articles/s41593-023-01316-5. Acesso em: 8 nov. 2025.

NICHOLS, D. E. Psychedelics. Pharmacological Reviews, v. 68, n. 2, p. 264-355, 2016. DOI: https://doi.org/10.1124/pr.115.011478. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0031699724011827. Acesso em: 8 nov. 2025.

NIH PubChem. Psilocybin [Internet]. Bethesda (MD): National Center for Biotechnology Information; 2004-2025 [citado em 10 nov. 2025]. Disponível em: https://pubchem.ncbi.nlm.nih.gov/compound/Psilocybin. Acesso em: 4 abr. 2025a.

NIH PubChem. Serotonin [Internet]. Bethesda (MD): National Center for Biotechnology Information; 2004-2025 [citado em 10 nov. 2025]. Disponível em: https://pubchem.ncbi.nlm.nih.gov/compound/Serotonin. Acesso em: 4 abr. 2025b.

NUTT, D. Psychedelic drugs: a new era in psychiatry? Dialogues in Clinical Neuroscience, v. 21, n. 2, p. 139-147, 2019. DOI: https://doi.org/10.31887/DCNS.2019.21.2/dnutt. Disponível em: https://www.tandfonline.com/doi/full/10.31887/DCNS.2019.21.2/dnutt. Acesso em: 8 nov. 2025.

OLSEN, A. S.; LYKKEBO-VALLØE, A.; OZENNE, B.; MADSEN, M. K.; STENBÆK, D. S.; ARMAND, S.; MØRUP, M.; GANZ, M.; KNUDSEN, G. M.; FISHER, P. M. Psilocybin modulation of time-varying functional connectivity is associated with plasma psilocin and subjective effects. NeuroImage, v. 264, 119716, 2022. DOI: https://doi.org/10.1016/j.neuroimage.2022.119716. Disponível em: https://pubmed.ncbi.nlm.nih.gov/36341951/. Acesso em: 8 nov. 2025

O'REARDON, J. P.; FONTECHA, J. F.; CRISTANCHO, M. A.; NEWMAN, S. Unexpected reduction in migraine and psychogenic headaches following rTMS treatment for major depression: a report of two cases. CNS Spectrums, v. 12, n. 12, p. 921-925, 2007. DOI: https://doi.org/10.1017/S1092852900015716. Disponível em: https://www.cambridge.org/core/journals/cns-spectrums/article/abs/unexpected-reduction-in-migraine-and-psychogenic-headaches-following-rtms-treatment-for-major-depression-a-report-of-two-cases/4D37211F27D17F70B9453BA5EB2C06B6. Acesso em: 8 nov. 2025.

OPAS. ORGANIZAÇÃO PAN-AMERICANA DA SAÚDE. Depressão. Brasília, 2022.

PACHECO, A. T.; OLSON, R. J.; GARZA, G.; MOGHADDAM, B. Acute psilocybin enhances cognitive flexibility in rats. Neuropsychopharmacology, v. 48, n. 7, p. 1011-1020, 2023. DOI: https://doi.org/10.1038/s41386-023-01545-z. Disponível em: https://www.nature.com/articles/s41386-023-01545-z. Acesso em: 8 nov. 2025.

PARIANTE, C. M.; LIGHTMAN, S. L. The HPA axis in major depression. Trends in Neurosciences, v. 31, n. 9, p. 464-468, 2008. DOI: https://doi.org/10.1016/j.tins.2008.06.006. Disponível em: https://www.sciencedirect.com/science/article/pii/S0166223608001641. Acesso em: 8 nov. 2025.

PASSIE, T.; SEIFERT, J.; SCHNEIDER, U.; EMRICH, H. M. The pharmacology of psilocybin. Addiction Biology, v. 7, n. 4, p. 357-364, 2002. DOI: https://doi.org/10.1080/1355621021000005937. Disponível em: https://onlinelibrary.wiley.com/doi/10.1080/1355621021000005937. Acesso em: 8 nov. 2025.

PINHO, M.; MARTINS, D. O.; SANTOS, M. F.; COUTINHO, F. When addressing trauma makes a difference: A Case Report of Undiagnosed Complex Post-traumatic Stress Disorder. Cureus, v. 16, n. 1, e51640, 2024. DOI: https://doi.org/10.7759/cureus.51640. Disponível em: https://www.cureus.com/articles/218296-when-addressing-trauma-makes-a-difference-a-case-report-of-undiagnosed-complex-post-traumatic-stress-disorder#!/. Acesso em: 8 nov. 2025.

POPIK, P.; HOGENDORF, A.; BUGNO, R.; KHOO, S. Y.-S.; ZAJDEL, P.; MALIKOWSKA-RACIA, N.; NIKIFORUK, A.; GOLEBIOWSKA, J. Effects of ketamine optical isomers, psilocybin and related compounds on cognition in rats. Psychopharmacology, v. 239, n. 6, p. 1689-1703, 2022. DOI: https://doi.org/10.1007/s00213-021-06020-5. Disponível em: https://link.springer.com/article/10.1007/s00213-021-06020-5. Acesso em: 8 nov. 2025.

REIFF, C. M.; RICHMAN, E. E.; NEMEROFF, C. B.; CARPENTER, L. L.; WIDGE, A. S.; RODRIGUEZ, C. I.; KALIN, N. H.; MCDONALD, W. M. Psychedelics and psychedelic-assisted psychotherapy. American Journal of Psychiatry, v. 177, n. 5, p. 391-410, 2020. DOI: https://doi.org/10.1176/appi.ajp.2019.19010035. Disponível em: https://psychiatryonline.org/doi/10.1176/appi.ajp.2019.19010035. Acesso em: 17 maio 2025.

ROSS, S.; BOSSIS, A.; GUSS, J.; AGIN-LIEBES, G.; MALONE, T.; COHEN, B.; MENNENGA, S. E.; BELSER, A.; KALLIONTZI, K.; BABB, J.; SU, Z.; CORBY, P.; SCHMIDT, B. L. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, v. 30, n. 12, p. 1165-1180, 2016. DOI: https://doi.org/10.1177/0269881116675512. Disponível em: https://journals.sagepub.com/doi/10.1177/0269881116675512. Acesso em: 8 nov. 2025.

RYGULA, R.; PIKSA, M.; CIESLIK-STARKIEWICZ, A. Cognitive, psychological, and pharmacological correlates of susceptibility to (mis)information: Why we believe and how we resist. Neuroscience & Biobehavioral Reviews, v. 177, 106339, 2025. DOI: https://doi.org/10.1016/j.neubiorev.2025.106339. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0149763425003409. Acesso em: 8 nov. 2025.

SAKLOTH, F.; LEGGETT, E.; MOERKE, M. J.; TOWNSEND, E. A.; BANKS, M. L.; NEGUS, S. S. Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats. Experimental and Clinical Psychopharmacology, v. 27, n. 3, p. 215-226, 2019. DOI: https://doi.org/10.1037/pha0000253. Disponível em: https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000253. Acesso em: 8 nov. 2025.

SANTOS, R. G.; BOUSO, J. C.; HALLAK, J. E. C. Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in end-stage cancer. BMC Psychiatry, v. 19, 321, 2019. DOI: https://doi.org/10.1186/s12888-019-2288-z. Disponível em: https://link.springer.com/article/10.1186/s12888-019-2288-z. Acesso em: 8 nov. 2025.

SHAO, L. X.; LIAO, C.; GREGG, I.; DAVOUDIAN, P. A.; SAVALIA, N. K.; DELAGARZA, K.; KWAN, A. C. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron, v. 109, n. 16, p. 2535-2544, 2021. DOI: https://doi.org/10.1016/j.neuron.2021.06.008. Disponível em: https://pubmed.ncbi.nlm.nih.gov/34228959/. Acesso em: 8 nov. 2025.

SOUERY, D.; AMSTERDAM, J.; MONTIGNY, C.; LECRUBIER, Y.; MONTGOMERY, S.; LIPP, O.; RACAGNI, G.; ZOHAR, J.; MENDLEWICZ, J. Treatment-resistant depression: methodological overview and operational criteria. European Neuropsychopharmacology, v. 6, n. 3, p. 145-151, 1999. Disponível em: https://pubmed.ncbi.nlm.nih.gov/10082232/. Acesso em: 8 abr. 2025.

SULLIVAN, P. F.; DALY, M. J.; O'DONOVAN, M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nature Reviews Genetics, v. 13, p. 537-551, 2012. DOI: https://doi.org/10.1038/nrg3240. Disponível em: https://www.nature.com/articles/nrg3240. Acesso em: 11 jun. 2025.

SWEATT, J. D. Experience-Dependent Epigenetic Modifications in the Central Nervous System. Biological Psychiatry, v. 65, n. 3, p. 191-197, 2009. DOI: https://doi.org/10.1016/j.biopsych.2008.09.002. Disponível em: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01089-5/fulltext. Acesso em: 11 jun. 2025.

TATARANU, L. G.; RIZEA, R. E. Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects. Brain sciences, v. 15, n. 4, 400, 2025. https://doi.org/10.3390/brainsci15040400. Disponível em: https://www.mdpi.com/2076-3425/15/4/400. Acesso em: 11 jun. 2025.

TRIVEDI, M. H.; PAPAKOSTAS, G. I.; SOUERY, D. Treatment-resistant depression. Journal of Clinical Psychiatry, v. 67, supl. 6, p. 16-22, 2006. Disponível em: https://www.psychiatrist.com/jcp/treatment-resistant-depression/. Acesso em: 9 abr. 2025.

TYLŠ, F.; PÁLENÍČEK, T.; HORÁČEK, J. Psilocybin: summary of knowledge and new perspectives. European Neuropsychopharmacology, v. 24, n. 3, p. 342-356, 2014. DOI: https://doi.org/10.1016/j.euroneuro.2013.12.006. Disponível em: https://www.sciencedirect.com/science/article/pii/S0924977X13003519. Acesso em: 11 jun. 2025.

UK ECT REVIEW GROUP. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. The Lancet, v. 361, n. 9360, p. 799-808, 2003. DOI: https://doi.org/10.1016/S0140-6736(03)12705-5. Disponível em: https://www.sciencedirect.com/science/article/pii/S0140673603127055. Acesso em: 11 jun. 2025.

VOLLENWEIDER, F. X.; KOMETER, M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, v. 11, p. 642-651, 2010. DOI: https://doi.org/10.1038/nrn2884. Disponível em: https://www.nature.com/articles/nrn2884. Acesso em: 11 jun. 2025.

WATTS, R.; LUOMA, J. B. The use of the psychological flexibility model to support psychedelic-assisted therapy. Journal of Contextual Behavioral Science, v. 15, p. 92-102, 2020. DOI: https://doi.org/10.1016/j.jcbs.2019.12.004. Disponível em: https://www.sciencedirect.com/science/article/pii/S2212144719301140. Acesso em: 11 jun. 2025.

WHITTEMORE, R.; KNAFL, K. The integrative review: updated methodology. Journal of advanced nursing, v. 52, n. 5, p. 546-553, 2005. DOI: https://doi.org/10.1111/j.1365-2648.2005.03621.x. Disponível em: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2648.2005.03621.x. Acesso em: 26 jun. 2026.

WOJTAS, A.; BYSIEK, A.; WAWRZCZAK-BARGIELA, A.; MAĆKOWIAK, M.; GOŁEMBIOWSKA, K. Limbic system response to psilocybin and ketamine administration in rats: A Neurochemical and Behavioral Study. International Journal of Molecular Sciences, v. 25, n. 1, 100, 2024. DOI: https://doi.org/10.3390/ijms25010100. Disponível em: https://www.mdpi.com/1422-0067/25/1/100. Acesso em: 8 nov. 2025.

WOJTAS, A.; BYSIEK, A.; WAWRZCZAK-BARGIELA, A.; SZYCH, Z.; MAJCHER-MAŚLANKA, I.; HERIAN, M.; MAĆKOWIAK, M.; GOŁEMBIOWSKA, K. Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior. International Journal of Molecular Sciences, v. 23, n. 12, 6713, 2022. DOI: https://doi.org/10.3390/ijms23126713. Disponível em: https://www.mdpi.com/1422-0067/23/12/6713. Acesso em: 8 nov. 2025.

WHO. WORLD HEALTH ORGANIZATION. Depression and other common mental disorders: global health estimates. Geneva: WHO, 2017. Disponível em: https://iris.who.int/handle/10665/254610. Acesso em: 2 abr. 2025.

WHO. WORLD HEALTH ORGANIZATION. World mental health report: transforming mental health for all. Geneva: WHO, 2023. Disponível em: https://www.who.int/publications/i/item/9789240049338. Acesso em: 2 abr. 2025.

YANG, J.; TONG, P.; DONG, L. P.; SHI, Y. H. A novel approach to investigate the mechanism of electroconvulsive therapy in the treatment of major depression disorder: Diffusion kurtosis imaging. Journal of Psychiatric Research, v. 179, p. 372-378, 2024. Disponível em: https://pubmed.ncbi.nlm.nih.gov/39368399/. Acesso em: 8 nov. 2025.

YU, Z.; BURBACK, L.; WINKLER, O.; XU, L.; DENNETT, L.; VERMETTEN, E.; GREENSHAW, A.; LI, X.-M.; MILNE, M.; WANG, F.; CAO, B.; WINSHIP, I. R.; ZHANG, Y.; CHAN, A. W. Alterations in brain network connectivity and subjective experience induced by psychedelics: a scoping review. Frontiers in Psychiatry, v. 15, 1386321, 2024. DOI: https://doi.org/10.3389/fpsyt.2024.1386321. Disponível em: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1386321/full. Acesso em: 8 nov. 2025.

ZARATE JUNIOR, C. A.; SINGH, J. B.; CARLSON, P. J.; BRUTSCHE, N. E.; AMELI, R.; LUCKENBAUGH, D. A.; CHARNEY, D. S.; MANJI, H. K. A randomized trial of an NMDA antagonist in treatment-resistant major depression. Archives of General Psychiatry, v. 63, n. 8, p. 856-864, 2006. Disponível em: https://pubmed.ncbi.nlm.nih.gov/16894061/. Acesso em: 26 ago. 2026.

Downloads

Publicado

31-08-2026

Edição

Seção

Artigos de revisão

Como Citar

CASTRO, Leticia Almeida; SIMÕES JÚNIOR, André Luiz Anjos; SIMÕES, Guilherme Gianizeli Corradi; SOUZA, Vagner Rocha Simonin; PEREIRA, Lucas Luís Meigre Dias; LACERDA, Ariely Lirio Sousa; SILVA, Cristiane Lyrio. Psilocibina e neuroplasticidade: novas perspectivas terapêuticas para depressão resistente. Revista Vértices, [S. l.], v. 28, n. 2, p. e28223658, 2026. DOI: 10.19180/1809-2667.v28n22026.23658. Disponível em: https://editoraessentia.iff.edu.br/index.php/vertices/article/view/23658.. Acesso em: 4 set. 2026.